Lab Notes: Milk Does a Pancreas Good

This week in Lab Notes, discover how milk may rejuvenate pancreatic islet cells to help manage diabetes. Plus the "dumbing" effects of anesthesia and curing well groomed mice with OCD.

For Diabetes, Got Milk?

The whey protein component of milk may help blood glucose regulation, according to a series of experiments looking for the mechanism behind lower type 2 diabetes rates found with higher milk consumption.

Pancreatic cells released more insulin when presented with more intact or partially-digested proteins from whey, Richard J. FitzGerald, of the University of Limerick, in Ireland, and colleagues reported in the Journal of Nutrition.

Diabetic obese mice fed the proteins had better glucose control than those that got a standard diet. The milk components also appeared to restore pancreatic islet cells' capacity to secrete insulin.

While further research is needed, milk "may be useful in diabetes management," the researchers concluded.

-- Crystal Phend

Numb and Dumb

Anesthesia's neurotoxic effects on the brain depend on the age of brain neurons, not the age of the brain, a mice study in the Annals of Neurology found.

In newborn mice, whose developing brains are continually generating new neurons, exposure to anesthesia caused widespread cell death in forebrain structures, while barely affecting the dentate gyrus and the olfactory bulb.

However, in juvenile and young adult mice, where neuron production has slowed considerably, the affects of anesthesia were minimal in the forebrain structures but more widespread in the dentate gyrus and the olfactory bulb -- two regions known to produce new neurons later in life.

Prenatal exposure to anesthesia would therefore have the greatest impact on forebrain neurons, while postnatal exposure could alter brain structure in the dentate gyrus, which is associated with learning and memory, according to Andreas Loepke, MD, PhD, of Cincinnati Children's Hospital Medical Center, and colleagues.

Isolated activation of the circuits produced no repetitive behaviors, but brief periods of stimulation over multiple consecutive days led to repetitive grooming behavior in the mice. Treatment with fluoxetine, a drug commonly used for OCD, abolished the behavior, as reported in the June 7 issue of Science.

The findings could have relevance to development of new, more effective therapies for OCD, according to Susanne Ahmari, MD, PhD, of Columbia University in New York City.

"Repeated hyperstimulation led to a marked progressive increase in light-evoked firing paralleling the increase in grooming, suggesting plasticity at the orbitofrontal cortex-ventromedial striatum (OFC-VMS) synapses that builds over days," they concluded. "We speculate that brief episodes of light-induced activity leads to long-lasting changes that prime OFC-VMS synapses, decreasing the activation threshold during subsequent bouts of stimulation."

The observations came from studies involving a technique known as optogenetics, which involves use of fast light-activated channels and enzymes that facilitate precise manipulation of electrical and biochemical events in specific neurons and neuronal circuits.

-- Charles Bankhead

Barring TB from the Brain

The bacille Calmette-Guerin (BCG) vaccine against tuberculosis is recommended for all newborns in places with high TB burden, mainly to prevent severe forms of the disease, such as meningitis, in infancy. But the performance of the vaccine against TB meningitis is variable, according to researchers led by Sanjay Jain, MD, of Johns Hopkins University School of Medicine.

In PLOS ONE, they noted that a TB protein dubbed PknD plays a central role when the pathogen invades the central nervous system. A subunit vaccine against PknD, they hypothesized, might stop TB from crossing the blood-brain barrier.

To test the idea, they inoculated infant guinea pigs with placebo, BCG, or the PknD vaccine and exposed them to airborne TB. Compared with placebo, BCG significantly limited TB in the lungs and disseminated disease in the brain, at P=0.01. The PknD vaccine had little or no effect on TB in the lungs, but did also reduce the burden of the disease in the brain significantly (also at P=0.01) and was not different in that setting from the BCG vaccine.

If results are similar in humans, the researchers argue, the vaccine might be used to boost BCG or in cases where BCG can't be used -- such as in babies with compromised immune systems -- as a substitute.

Rat models of fetal alcohol spectrum disorder experienced social interaction deficits through altered hippocampal expression of several genes in autism spectrum disorder, namely Gabrb3, Ube3a, Mecp2, and Slc25a12, according to Eva Redei, PhD, of Northwestern University in Chicago, and colleagues.

Rats were randomized to a control diet, a nutritional control pair-fed diet, ethanol, or an ethanol diet supplemented with 0.3, 1.5, or 7.5 mg/L of thyroxine, while their offspring were tested for social behavior and memory.

In addition to the social interaction deficits, rats whose parents were on the ethanol diet had decreased hippocampal Nr2b and Dio3, as well as decreased Rasgrf1.

In a statement, Redei cautioned that human studies would need to confirm the link between the two conditions, and that thyroid supplementation would be effective as a prophylactic in deficits associated with fetal alcohol spectrum disorder.

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